Zestoretic

Description

ZESTORETIC (Lisinopril and Hydrochlorothiazide) is a combination medication that includes lisinopril, an angiotensin converting enzyme (ACE) inhibitor, and hydrochlorothiazide, a diuretic. Lisinopril, USP is a synthetic peptide derivative, chemically designated as (S)-1-N2-(1-carboxy-3-phenylpropyl)-L-lysyl-L-proline dihydrate, with an empirical formula of C21H31N3O5·2H2O and a molecular weight of 441.53. It appears as a white to off-white crystalline powder, soluble in water, sparingly soluble in methanol, and practically insoluble in ethanol.

Hydrochlorothiazide, USP is identified as 6-chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide, with an empirical formula of C7H8ClN3O4S2 and a molecular weight of 297.72. This compound is a white or practically white crystalline powder, slightly soluble in water, and freely soluble in sodium hydroxide solution.

ZESTORETIC is formulated for oral administration and is available in three tablet combinations: ZESTORETIC 10-12.5, which contains 10 mg of lisinopril and 12.5 mg of hydrochlorothiazide; ZESTORETIC 20-12.5, which contains 20 mg of lisinopril and 12.5 mg of hydrochlorothiazide; and ZESTORETIC 20-25, which contains 20 mg of lisinopril and 25 mg of hydrochlorothiazide. The inactive ingredients vary by tablet formulation, including calcium phosphate, magnesium stearate, mannitol, corn starch, and color additives such as red and yellow ferric oxide.

Uses and Indications

ZESTORETIC is indicated for the treatment of hypertension to lower blood pressure. Effective management of high blood pressure is essential for reducing the risk of both fatal and non-fatal cardiovascular events, primarily strokes and myocardial infarctions.

Control of hypertension should be integrated into a comprehensive cardiovascular risk management strategy, which includes lipid control, diabetes management, antithrombotic therapy, smoking cessation, regular exercise, and limited sodium intake. It is important to note that many patients may require more than one antihypertensive medication to achieve their blood pressure goals.

Numerous antihypertensive agents have demonstrated efficacy in randomized controlled trials, showing a reduction in cardiovascular morbidity and mortality, with blood pressure reduction being a significant contributor to these benefits. The most substantial and consistent cardiovascular outcome benefit observed is a reduction in the risk of stroke, alongside reductions in myocardial infarction and cardiovascular mortality.

Elevated systolic or diastolic blood pressure is associated with increased cardiovascular risk, and even modest reductions in severe hypertension can yield considerable benefits. The relative risk reduction associated with blood pressure lowering is consistent across various populations with differing absolute risks, with patients at higher risk—such as those with diabetes or hyperlipidemia—experiencing greater absolute benefits, regardless of their hypertension status.

It is also noted that some antihypertensive medications may exhibit smaller blood pressure-lowering effects when used as monotherapy in black patients. Additionally, many of these agents have other approved indications and therapeutic effects, including those related to angina, heart failure, or diabetic kidney disease.

Dosage and Administration

Lisinopril monotherapy is indicated at once-daily doses ranging from 10 mg to 80 mg. Hydrochlorothiazide monotherapy is effective at daily doses between 12.5 mg and 50 mg.

For patients requiring combination therapy with lisinopril and hydrochlorothiazide, the recommended dosing is as follows: lisinopril should be administered in doses of 10 mg to 80 mg, while hydrochlorothiazide should be given in doses of 6.25 mg to 50 mg.

In cases where a patient's blood pressure remains inadequately controlled with either monotherapy, a switch to a combination of lisinopril and hydrochlorothiazide may be considered. The initial combination doses can be either Lisinopril/HCTZ 10/12.5 or Lisinopril/HCTZ 20/12.5, depending on the current monotherapy dose.

Further adjustments to the doses of either or both components should be guided by clinical response, with blood pressure measurements taken at the interdosing interval. It is recommended that the hydrochlorothiazide dose not be increased until a period of 2 to 3 weeks has elapsed to assess the patient's response adequately.

If the diuretic cannot be discontinued, an initial dose of 5 mg of lisinopril should be administered under medical supervision for at least two hours, with monitoring until blood pressure has stabilized for an additional hour.

Therapeutic regimens involving lisinopril and hydrochlorothiazide do not require adjustments based on renal function, provided the patient's creatinine clearance is greater than 30 mL/min/1.7 m² (approximately serum creatinine ≤3 mg/dL or 265 μmol/L).

Contraindications

ZESTORETIC is contraindicated in patients with hypersensitivity to the product. It is also contraindicated in individuals with a history of angioedema associated with prior treatment using an angiotensin-converting enzyme inhibitor, as well as in those with hereditary or idiopathic angioedema.

Patients with anuria or hypersensitivity to other sulfonamide-derived drugs should not use ZESTORETIC due to the hydrochlorothiazide component. Additionally, ZESTORETIC is contraindicated in combination with neprilysin inhibitors, such as sacubitril; administration should not occur within 36 hours of switching to or from sacubitril/valsartan.

Co-administration of aliskiren with ZESTORETIC is contraindicated in patients with diabetes.

Warnings and Precautions

Patients receiving ACE inhibitors, including ZESTORETIC, may experience a range of adverse reactions, some of which can be serious. Anaphylactoid reactions, including those potentially related to the medication, have been documented. Healthcare professionals should remain vigilant for signs of these reactions, particularly in patients undergoing desensitization treatment or those exposed to high-flux dialysis membranes, as life-threatening anaphylactoid reactions have been reported in these contexts.

Angioedema is another significant concern associated with ACE inhibitors. Both head and neck angioedema and intestinal angioedema have been observed. Angioedema can occur at any time during treatment, necessitating the immediate discontinuation of ZESTORETIC and the initiation of appropriate therapy and monitoring until the resolution of symptoms. Intestinal angioedema may present with abdominal pain, which typically resolves upon cessation of the ACE inhibitor.

Hypotension is a potential risk, particularly in patients who are salt or volume-depleted. Initiating therapy in patients with severe congestive heart failure should be conducted under close medical supervision to mitigate the risk of excessive hypotension. Additionally, rare cases of leukopenia, neutropenia, and agranulocytosis have been reported, warranting periodic monitoring of white blood cell counts, especially in patients with underlying collagen vascular or renal diseases.

Hepatic failure has been infrequently associated with ACE inhibitors, potentially progressing to fulminant hepatic necrosis and death. If a patient exhibits jaundice or significant elevations in hepatic enzymes, the ACE inhibitor should be discontinued immediately.

General precautions should be taken when prescribing ZESTORETIC to patients with aortic stenosis or hypertrophic cardiomyopathy, as caution is advised in those with left ventricular outflow tract obstruction. Additionally, renal function may be affected in susceptible individuals; therefore, monitoring of renal function is recommended during the initial weeks of therapy. Hyperkalemia has been observed in approximately 1.4% of hypertensive patients treated with lisinopril and hydrochlorothiazide, necessitating cautious use alongside other agents that may elevate potassium levels. A persistent nonproductive cough has also been reported with ACE inhibitors, which should be communicated to patients.

Laboratory tests are essential for safe management. Periodic assessment of serum electrolytes is recommended to detect potential imbalances, and renal function should be evaluated in hypertensive patients. Serum and urine electrolyte determinations are particularly critical in cases of excessive vomiting or when patients are receiving parenteral fluids.

In the event of severe reactions, particularly those involving the tongue, glottis, or larynx that may lead to airway obstruction, immediate medical intervention is required. Subcutaneous epinephrine solution (1:1000) should be administered (0.3 mL to 0.5 mL), along with any necessary measures to ensure airway patency.

Patients should be advised to seek immediate medical attention if hypotension occurs. In such cases, they should be positioned supine, and intravenous infusion of normal saline may be necessary to stabilize their condition.

Side Effects

Adverse reactions have been observed in patients receiving treatment, with varying degrees of seriousness and frequency.

Common adverse reactions occurring in 1% or more of participants include dizziness (7.5%), headache (5.2%), cough (3.9%), fatigue (3.7%), and orthostatic effects (3.2%). Other frequently reported reactions include diarrhea (2.5%), nausea (2.2%), upper respiratory infection (2.2%), muscle cramps (2.0%), and asthenia (1.8%). Additional common reactions noted are paresthesia (1.5%), hypotension (1.4%), vomiting (1.4%), dyspepsia (1.3%), rash (1.2%), and impotence (1.2%).

In addition to these common reactions, other adverse events have been reported across various systems. Cardiovascular effects include palpitations and orthostatic hypotension. Gastrointestinal disturbances may manifest as gastrointestinal cramps, dry mouth, constipation, and heartburn. Musculoskeletal complaints such as back pain, shoulder pain, knee pain, and myalgia have also been noted.

Nervous and psychiatric effects include decreased libido, vertigo, depression, and somnolence. Respiratory issues may present as common cold, nasal congestion, influenza, bronchitis, pharyngeal pain, dyspnea, pulmonary congestion, chronic sinusitis, and allergic rhinitis. Skin reactions can include flushing, pruritus, skin inflammation, diaphoresis, and in rare cases, cutaneous pseudolymphoma. Special senses may be affected, leading to blurred vision and tinnitus. Urogenital adverse reactions include urinary tract infections.

Serious adverse reactions warrant particular attention. Angioedema, affecting the face, extremities, lips, tongue, glottis, and/or larynx, has been reported, with rare instances of intestinal angioedema noted in post-marketing experience. Hypotension was observed in 1.4% of patients during clinical trials, with orthostatic hypotension occurring in 0.5% and syncope in 0.8%. A persistent nonproductive cough has been associated with ACE inhibitors, typically resolving upon discontinuation of therapy. Rare cases of leukopenia, neutropenia, and agranulocytosis have been documented, alongside reports of hepatic failure linked to cholestatic jaundice or hepatitis that may progress to fulminant hepatic necrosis.

Post-marketing experience has revealed an increased risk of non-melanoma skin cancer, particularly squamous cell carcinoma, in white patients taking large cumulative doses of hydrochlorothiazide.

Drug Interactions

Patients receiving lisinopril and hydrochlorothiazide should be aware of several significant drug interactions that may affect treatment outcomes and safety.

Pharmacodynamic Interactions

• Diuretics and Lisinopril: Patients on diuretics may experience an excessive reduction in blood pressure upon initiation of lisinopril therapy. To minimize the risk of hypotension, it is advisable to discontinue the diuretic or increase salt intake prior to starting lisinopril.

• NSAIDs and Lisinopril: Co-administration of non-steroidal anti-inflammatory drugs (NSAIDs), including selective COX-2 inhibitors, with lisinopril may lead to renal function deterioration, including potential acute renal failure, particularly in elderly, volume-depleted patients or those with pre-existing renal impairment. Regular monitoring of renal function is recommended. Additionally, the antihypertensive effect of lisinopril may be diminished by NSAIDs.

• Hydrochlorothiazide and Alcohol/Narcotics: The use of alcohol, barbiturates, or narcotics may enhance the risk of orthostatic hypotension in patients taking hydrochlorothiazide.

• Corticosteroids and Hydrochlorothiazide: Concurrent use of corticosteroids or ACTH may exacerbate electrolyte depletion, particularly hypokalemia.

• Lithium and Diuretics: The combination of lithium with diuretics, including hydrochlorothiazide, is generally contraindicated due to the risk of reduced renal clearance and increased lithium toxicity. If co-administration is necessary, frequent monitoring of serum lithium levels is advised.

Pharmacokinetic Interactions

• ACE Inhibitors and mTOR Inhibitors: Patients receiving both ACE inhibitors, such as lisinopril, and mTOR inhibitors (e.g., temsirolimus, sirolimus, everolimus) may have an elevated risk of angioedema.

• Neprilysin Inhibitors and Lisinopril: The concomitant use of neprilysin inhibitors with lisinopril may increase the risk of angioedema.

• Absorption of Hydrochlorothiazide: The absorption of hydrochlorothiazide can be significantly impaired by cholestyramine and colestipol resins, which may reduce its therapeutic efficacy.

Combination Therapy Considerations

• Dual RAS Blockade: The combined use of RAS inhibitors, including angiotensin receptor blockers, ACE inhibitors, or aliskiren, is associated with heightened risks of hypotension, hyperkalemia, and renal function changes compared to monotherapy. It is recommended to avoid this combination and to closely monitor blood pressure, renal function, and electrolyte levels in patients on ZESTORETIC and other RAS-affecting agents.

• Potassium Management: Lisinopril may attenuate potassium loss caused by thiazide diuretics. However, caution is warranted when using lisinopril with potassium-sparing diuretics, potassium supplements, or potassium-containing salt substitutes, as this may lead to significant increases in serum potassium levels.

• Antidiabetic Drugs and Hydrochlorothiazide: Dosage adjustments of antidiabetic medications (both oral agents and insulin) may be necessary when used concurrently with hydrochlorothiazide.

• Pressor Amines and Hydrochlorothiazide: There may be a decreased response to pressor amines (e.g., norepinephrine) when used with hydrochlorothiazide, although this is not sufficient to contraindicate their use.

• Skeletal Muscle Relaxants and Hydrochlorothiazide: Increased responsiveness to non-depolarizing skeletal muscle relaxants (e.g., tubocurarine) may occur with hydrochlorothiazide.

• Gold Therapy and ACE Inhibitors: Rare nitritoid reactions have been reported in patients receiving injectable gold (sodium aurothiomalate) in conjunction with ACE inhibitors.

Close monitoring and appropriate dosage adjustments are essential when managing patients on these medications to mitigate the risks associated with these interactions.

Packaging & NDC

The table below lists all NDC Code configurations of Zestoretic (lisinopril and hydrochlorothiazide), the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

Pediatric patients, particularly neonates with a history of in utero exposure to ZESTORETIC, may experience complications such as oliguria or hypotension. In such cases, it is crucial to provide support for blood pressure and renal perfusion. Interventions such as exchange transfusions or dialysis may be necessary to address hypotension and manage impaired renal function. Notably, lisinopril, a component of ZESTORETIC that crosses the placenta, has been effectively removed from neonatal circulation through peritoneal dialysis, which has shown some clinical benefit. Although theoretically, exchange transfusion may also facilitate removal, there is currently no clinical experience to support this procedure.

It is important to note that the safety and effectiveness of ZESTORETIC in pediatric patients have not been established. Therefore, caution is advised when considering its use in this population.

Geriatric Use

Clinical studies of ZESTORETIC did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. However, other reported clinical experience has not identified significant differences in responses between elderly patients and younger individuals.

In general, dose selection for geriatric patients should be approached with caution. It is advisable to start at the low end of the dosing range, taking into account the increased likelihood of decreased hepatic, renal, or cardiac function, as well as the presence of concomitant diseases or other drug therapies. Given that ZESTORETIC is substantially excreted by the kidneys, the risk of toxic reactions may be heightened in patients with impaired renal function.

Elderly patients are more prone to renal function decline; therefore, careful consideration should be given to dose selection in this population. Additionally, the evaluation of hypertensive elderly patients should always include an assessment of renal function to ensure safe and effective treatment.

Pregnancy

There were no adverse effects on reproductive performance observed in male and female rats treated with lisinopril at doses up to 300 mg/kg/day. Additionally, hydrochlorothiazide did not adversely affect the fertility of mice and rats of either sex in studies where these species were exposed to doses of up to 100 mg/kg and 4 mg/kg, respectively, prior to conception and throughout gestation.

While these findings suggest a lack of reproductive toxicity in animal studies, the relevance of these results to human pregnancy is not established. Therefore, healthcare professionals should consider the potential risks and benefits when prescribing this medication to pregnant patients or women of childbearing potential.

Lactation

It is not known whether lisinopril is excreted in human milk. However, studies in lactating rats have shown that the milk contains radioactivity following the administration of 14C lisinopril, with another study indicating that lisinopril was present in rat milk at levels comparable to plasma levels in the dams. Thiazides, which are components of ZESTORETIC, are known to appear in human milk.

Due to the potential for serious adverse reactions in breastfed infants from ACE inhibitors and hydrochlorothiazide, healthcare professionals should consider the risks and benefits when advising lactating mothers. A decision should be made regarding the discontinuation of nursing and/or the discontinuation of ZESTORETIC, taking into account the importance of the medication to the mother.

Renal Impairment

Patients with renal impairment should be treated with caution, particularly when using thiazides, as they may precipitate azotemia and lead to cumulative effects due to reduced kidney function. In severe renal disease, thiazides should be used judiciously.

Periodic monitoring of white blood cell counts is advisable for patients with collagen vascular disease and renal disease, as these patients may be at increased risk for agranulocytosis and bone marrow depression. Additionally, excessive hypotension has been observed in patients with severe congestive heart failure, regardless of renal status.

Patients receiving ACE inhibitors, including ZESTORETIC, may experience a range of adverse reactions, particularly those with renal impairment. Close monitoring is essential for patients on dialysis, as they are at risk for anaphylactoid reactions when treated with ACE inhibitors. Furthermore, patients with a history of angioedema unrelated to ACE inhibitor therapy may have an increased risk of angioedema while receiving these medications.

It is recommended that patients be closely monitored during the first two weeks of treatment and whenever there is an increase in the dose of lisinopril and/or diuretic. In cases of hypotension, the patient should be placed in a supine position and may require an intravenous infusion of normal saline.

Hepatic Impairment

Patients with hepatic impairment may experience an increased risk of adverse effects when treated with ACE inhibitors. Rarely, these medications have been associated with a syndrome that begins with cholestatic jaundice or hepatitis and can progress to fulminant hepatic necrosis, which may result in death. The underlying mechanism of this syndrome remains unclear.

In patients receiving ACE inhibitors, if jaundice or significant elevations in hepatic enzymes are observed, it is imperative to discontinue the ACE inhibitor immediately and ensure appropriate medical follow-up is provided.

Thiazide diuretics should be administered with caution in patients with impaired hepatic function or progressive liver disease. Minor alterations in fluid and electrolyte balance in these patients may precipitate hepatic coma, necessitating careful monitoring and potential dosage adjustments.

Overdosage

In the event of an overdosage with ZESTORETIC, specific treatment information is not available; therefore, management should be symptomatic and supportive. It is recommended that therapy with ZESTORETIC be discontinued, and the patient should be closely monitored for any adverse effects.

Recommended Actions

In cases of suspected overdosage, the following measures are suggested:

• Induction of emesis and/or gastric lavage may be considered to reduce the absorption of the drug.

• Correction of dehydration, electrolyte imbalances, and hypotension should be performed using established medical procedures.

Potential Symptoms

The most likely manifestation of overdosage is hypotension. In such cases, the standard treatment involves the intravenous infusion of normal saline solution to restore blood pressure.

Special Considerations

Animal studies indicate that a single oral dose of 20 g/kg did not result in lethality in rats; however, one out of twenty mice did not survive this dosage. This suggests variability in response among different species.

Additionally, it is important to note that lisinopril, one of the components of ZESTORETIC, can be effectively removed from the body through hemodialysis, which may be considered in severe cases of overdosage.

Healthcare professionals should remain vigilant and provide appropriate supportive care to manage any complications arising from overdosage.

Nonclinical Toxicology

Lisinopril and hydrochlorothiazide have been evaluated for their potential teratogenic effects, and no teratogenic effects were identified in the studies conducted. In terms of non-teratogenic effects, reproductive performance was unaffected in male and female rats treated with lisinopril at doses up to 300 mg/kg/day. Similarly, hydrochlorothiazide did not adversely impact fertility in mice and rats of either sex when administered dietary doses of up to 100 mg/kg and 4 mg/kg, respectively, prior to conception and throughout gestation.

Lisinopril, in combination with hydrochlorothiazide, demonstrated no mutagenic potential in microbial mutagen tests using Salmonella typhimurium (Ames test) and Escherichia coli, both with and without metabolic activation. Additionally, no mutagenic effects were observed in a forward mutation assay using Chinese hamster lung cells. The combination also did not induce DNA single strand breaks in an in vitro alkaline elution assay using rat hepatocytes. Furthermore, lisinopril did not result in increased chromosomal aberrations in in vitro tests conducted in Chinese hamster ovary cells or in in vivo studies involving mouse bone marrow.

Long-term studies indicated no evidence of tumorigenic effects associated with lisinopril when administered for 105 weeks to male and female rats at doses up to 90 mg/kg/day. Similarly, no carcinogenicity was observed in male and female mice treated with lisinopril for 92 weeks at doses up to 135 mg/kg/day. Hydrochlorothiazide was also found to be non-genotoxic in in vitro assays, including the Ames mutagenicity assay and the Chinese Hamster Ovary (CHO) test for chromosomal aberrations. However, it exhibited positive results in the in vitro CHO Sister Chromatid Exchange assay and the Mouse Lymphoma Cell assay for mutagenicity.

Two-year feeding studies in mice and rats provided no evidence of carcinogenic potential for hydrochlorothiazide in female mice or in male and female rats. However, the National Toxicology Program (NTP) reported equivocal evidence for hepatocarcinogenicity in male mice.

Postmarketing Experience

Postmarketing experience has identified an association between hydrochlorothiazide and an increased risk of non-melanoma skin cancer. Data from a study conducted within the Sentinel System indicate that this increased risk is primarily observed for squamous cell carcinoma (SCC), particularly among white patients who have received large cumulative doses of the medication. The overall population shows an approximate increase of 1 additional case of SCC per 16,000 patients per year. Notably, for white patients who have taken a cumulative dose of ≥50,000 mg, the risk escalates to approximately 1 additional case of SCC for every 6,700 patients per year.

Patient Counseling

Patients should be advised to report immediately any signs or symptoms suggesting angioedema, which may include swelling of the face, extremities, eyes, lips, or tongue, as well as difficulty in swallowing or breathing. They should be instructed to refrain from taking any additional doses of the medication until they have consulted with their prescribing physician.

Patients should be cautioned to report any instances of lightheadedness, particularly during the initial days of therapy. In the event of actual syncope, patients should be advised to discontinue the medication and seek guidance from their physician.

It is important to inform all patients that excessive perspiration and dehydration can lead to a significant drop in blood pressure due to reduced fluid volume. They should also be made aware that other factors contributing to volume depletion, such as vomiting or diarrhea, may similarly result in decreased blood pressure. Patients are encouraged to consult with their physician if they experience these conditions.

Patients should be instructed not to use salt substitutes that contain potassium without prior consultation with their physician.

Prompt reporting of any signs of infection, such as a sore throat or fever, is essential, as these may indicate leukopenia or neutropenia. Patients should be made aware of this potential risk.

Female patients of childbearing age should be informed about the implications of exposure to ZESTORETIC during pregnancy. Healthcare providers should discuss treatment options with women who are planning to become pregnant, and patients should be encouraged to report any pregnancies to their physicians as soon as possible.

Patients taking hydrochlorothiazide should be instructed to protect their skin from sun exposure and to undergo regular skin cancer screenings to monitor for any potential issues.

Storage and Handling

The product is supplied in various package configurations, with specific NDC numbers available upon request. It should be stored at a controlled room temperature, maintained between 20°C to 25°C (68°F to 77°F), in accordance with USP guidelines. It is essential to protect the product from excessive light and humidity to ensure its integrity and efficacy. Proper handling and storage conditions are critical for maintaining the quality of the product.

Additional Clinical Information

Periodic determination of serum electrolytes is recommended to detect potential electrolyte imbalances in patients, particularly during instances of excessive vomiting or when receiving parenteral fluids. Clinicians should also assess renal function as part of the evaluation for hypertensive patients.

Patients should be counseled to report any signs of angioedema, such as swelling of the face, extremities, or difficulty in breathing, and to refrain from taking additional medication until consulting their physician. They should be aware of the risk of lightheadedness, especially during the initial days of therapy, and discontinue use if syncope occurs. Patients must be informed that excessive perspiration and dehydration can lead to significant drops in blood pressure, and they should consult their physician if they experience volume depletion due to vomiting or diarrhea. Additionally, patients should avoid potassium-containing salt substitutes without prior consultation and report any signs of infection that may indicate leukopenia or neutropenia. Female patients of childbearing age should discuss the implications of ZESTORETIC exposure during pregnancy and report any pregnancies promptly. Those taking hydrochlorothiazide should be advised to protect their skin from sun exposure and undergo regular skin cancer screenings.

Postmarketing data indicate that hydrochlorothiazide is associated with an increased risk of non-melanoma skin cancer, particularly squamous cell carcinoma (SCC), especially in white patients receiving high cumulative doses. The overall risk for SCC is approximately one additional case per 16,000 patients per year, increasing to one additional case for every 6,700 patients per year in those taking a cumulative dose of 50,000 mg or more.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Zestoretic as submitted by Almatica Pharma Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)